Mark Anderson, MD, PhD
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Title(s) | Professor, Diabetes Center |
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School | School of Medicine |
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Phone | 415-502-8052 |
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vCard | Download vCard |
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Biography University of Chicago | M.D. | 1994 | Pritzker School of Medicine | University of Chicago | PhD | 1992 | Immunology |
| 2004 | | Pew Scholar | | 2009 | | Robert B. Friend and Michelle M. Friend Endowed Chair in Diabetes Research | | 2009 | | American Society of Clinical Investigation | UCSF | 2012 | | Byers Award in Basic Science | | 2016 | | American Association of Physicians |
Overview EDUCATION/CLINICAL TRAINING MD: MD, PhD, University of Chicago, 1994 Residency: University of Minnesota, MD, Internal Medicine, 1994-1997 Chief Resident, University of Minnesota 1997-1998 Fellowship: Massachusetts General Hospital, Adult Endocrinology, 1998-2001 Board Certification: Endocrinology and Metabolism, 2001, Renewed 2012
ACADEMIC INTERESTS The main research interest of our laboratory group is to examine the genetic control of autoimmune diseases to gain a better understanding of the mechanisms by which immune tolerance is broken. A major focus of our lab group is a human autoimmune syndrome called Autoimmune Polyglandular Syndrome Type 1 (APS1 or APECED), which is classically manifested by an autoimmune attack directed at multiple endocrine organs. This disease is inherited in a monogenic autosomal recessive fashion and the defective gene has been identified and is called Aire (for autoimmune regulator). Aire knockout mice, like their human counterparts, develop an autoimmune disease that is targeted to multiple organs. Through the use of the mouse model we, along with others, have determined that Aire plays an important role in immune tolerance by promoting the expression of many self proteins in specialized antigen presenting cells in the thymus called medullary epithelial cells (mTEC’s).
Recently, we have determined that this process is not only critical in the thymus, but also in peripheral lymphoid organs. Current studies in the lab are directed at further understanding the relative contribution of specialized Aire-expressing cells to immune tolerance in multiple autoimmune disease models. In addition to these ongoing studies, our laboratory is also interested the pathogenesis of autoimmune diabetes and in developing other models of autoimmune disease by using transgenic, knockout, and knock-in approaches.
CLINICAL INTERESTS: Type 1 diabetes and associated autoimmune disorders
Appointments: 415-353-2350
Research ORNG Applications Bibliographic
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Calderon D, Nguyen MLT, Mezger A, Kathiria A, Müller F, Nguyen V, Lescano N, Wu B, Trombetta J, Ribado JV, Knowles DA, Gao Z, Blaeschke F, Parent AV, Burt TD, Anderson MS, Criswell LA, Greenleaf WJ, Marson A, Pritchard JK. Landscape of stimulation-responsive chromatin across diverse human immune cells. Nat Genet. 2019 Sep 30. PMID: 31570894.
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Sin JH, Zuckerman C, Cortez JT, Eckalbar WL, Erle DJ, Anderson MS, Waterfield MR. The epigenetic regulator ATF7ip inhibits Il2 expression, regulating Th17 responses. J Exp Med. 2019 Sep 02; 216(9):2024-2037. PMID: 31217192.
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Su MA, Anderson MS. Pulling RANK on Cancer: Blocking Aire-Mediated Central Tolerance to Enhance Immunotherapy. Cancer Immunol Res. 2019 Jun; 7(6):854-859. PMID: 31160305.
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Simeonov DR, Brandt AJ, Chan AY, Cortez JT, Li Z, Woo JM, Lee Y, Carvalho CMB, Indart AC, Roth TL, Zou J, May AP, Lupski JR, Anderson MS, Buaas FW, Rokhsar DS, Marson A. A large CRISPR-induced bystander mutation causes immune dysregulation. Commun Biol. 2019; 2:70. PMID: 30793048.
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Van Gool F, Nguyen MLT, Mumbach MR, Satpathy AT, Rosenthal WL, Giacometti S, Le DT, Liu W, Brusko TM, Anderson MS, Rudensky AY, Marson A, Chang HY, Bluestone JA. A Mutation in the Transcription Factor Foxp3 Drives T Helper 2 Effector Function in Regulatory T Cells. Immunity. 2019 02 19; 50(2):362-377.e6. PMID: 30709738.
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Miller CN, Proekt I, von Moltke J, Wells KL, Rajpurkar AR, Wang H, Rattay K, Khan IS, Metzger TC, Pollack JL, Fries AC, Lwin WW, Wigton EJ, Parent AV, Kyewski B, Erle DJ, Hogquist KA, Steinmetz LM, Locksley RM, Anderson MS. Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development. Nature. 2018 07; 559(7715):627-631. PMID: 30022164.
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Nadjsombati MS, McGinty JW, Lyons-Cohen MR, Jaffe JB, DiPeso L, Schneider C, Miller CN, Pollack JL, Nagana Gowda GA, Fontana MF, Erle DJ, Anderson MS, Locksley RM, Raftery D, von Moltke J. Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit. Immunity. 2018 07 17; 49(1):33-41.e7. PMID: 30021144.
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Simeonov DR, Gowen BG, Boontanrart M, Roth TL, Gagnon JD, Mumbach MR, Satpathy AT, Lee Y, Bray NL, Chan AY, Lituiev DS, Nguyen ML, Gate RE, Subramaniam M, Li Z, Woo JM, Mitros T, Ray GJ, Curie GL, Naddaf N, Chu JS, Ma H, Boyer E, Van Gool F, Huang H, Liu R, Tobin VR, Schumann K, Daly MJ, Farh KK, Ansel KM, Ye CJ, Greenleaf WJ, Anderson MS, Bluestone JA, Chang HY, Corn JE, Marson A. Author Correction: Discovery of stimulation-responsive immune enhancers with CRISPR activation. Nature. 2018 07; 559(7715):E13. PMID: 29899441.
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Cheng M, Anderson MS. Thymic tolerance as a key brake on autoimmunity. Nat Immunol. 2018 07; 19(7):659-664. PMID: 29925986.
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Perry JSA, Russler-Germain EV, Zhou YW, Purtha W, Cooper ML, Choi J, Schroeder MA, Salazar V, Egawa T, Lee BC, Abumrad NA, Kim BS, Anderson MS, DiPersio JF, Hsieh CS. Transfer of Cell-Surface Antigens by Scavenger Receptor CD36 Promotes Thymic Regulatory T Cell Receptor Repertoire Development and Allo-tolerance. Immunity. 2018 06 19; 48(6):1271. PMID: 29924978.
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Perry JSA, Russler-Germain EV, Zhou YW, Purtha W, Cooper ML, Choi J, Schroeder MA, Salazar V, Egawa T, Lee BC, Abumrad NA, Kim BS, Anderson MS, DiPersio JF, Hsieh CS. Transfer of Cell-Surface Antigens by Scavenger Receptor CD36 Promotes Thymic Regulatory T Cell Receptor Repertoire Development and Allo-tolerance. Immunity. 2018 05 15; 48(5):923-936.e4. PMID: 29752065.
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Spence A, Purtha W, Tam J, Dong S, Kim Y, Ju CH, Sterling T, Nakayama M, Robinson WH, Bluestone JA, Anderson MS, Tang Q. Revealing the specificity of regulatory T cells in murine autoimmune diabetes. Proc Natl Acad Sci U S A. 2018 05 15; 115(20):5265-5270. PMID: 29712852.
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Proekt I, Miller CN, Lionakis MS, Anderson MS. Insights into immune tolerance from AIRE deficiency. Curr Opin Immunol. 2017 Dec; 49:71-78. PMID: 29065385.
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Michel C, Miller CN, Küchler R, Brors B, Anderson MS, Kyewski B, Pinto S. Revisiting the Road Map of Medullary Thymic Epithelial Cell Differentiation. J Immunol. 2017 11 15; 199(10):3488-3503. PMID: 28993517.
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Bakhru P, Zhu ML, Wang HH, Hong LK, Khan I, Mouchess M, Gulati AS, Starmer J, Hou Y, Sailer D, Lee S, Zhao F, Kirkwood JM, Moschos S, Fong L, Anderson MS, Su MA. Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity. JCI Insight. 2017 09 21; 2(18). PMID: 28931755.
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Simeonov DR, Gowen BG, Boontanrart M, Roth TL, Gagnon JD, Mumbach MR, Satpathy AT, Lee Y, Bray NL, Chan AY, Lituiev DS, Nguyen ML, Gate RE, Subramaniam M, Li Z, Woo JM, Mitros T, Ray GJ, Curie GL, Naddaf N, Chu JS, Ma H, Boyer E, Van Gool F, Huang H, Liu R, Tobin VR, Schumann K, Daly MJ, Farh KK, Ansel KM, Ye CJ, Greenleaf WJ, Anderson MS, Bluestone JA, Chang HY, Corn JE, Marson A. Discovery of stimulation-responsive immune enhancers with CRISPR activation. Nature. 2017 09 07; 549(7670):111-115. PMID: 28854172.
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Sagan SA, Winger RC, Cruz-Herranz A, Nelson PA, Hagberg S, Miller CN, Spencer CM, Ho PP, Bennett JL, Levy M, Levin MH, Verkman AS, Steinman L, Green AJ, Anderson MS, Sobel RA, Zamvil SS. Tolerance checkpoint bypass permits emergence of pathogenic T cells to neuromyelitis optica autoantigen aquaporin-4. Proc Natl Acad Sci U S A. 2016 12 20; 113(51):14781-14786. PMID: 27940915.
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Proekt I, Miller CN, Jeanne M, Fasano KJ, Moon JJ, Lowell CA, Gould DB, Anderson MS, DeFranco AL. LYN- and AIRE-mediated tolerance checkpoint defects synergize to trigger organ-specific autoimmunity. J Clin Invest. 2016 10 03; 126(10):3758-3771. PMID: 27571405.
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Anderson MS, Su MA. AIRE expands: new roles in immune tolerance and beyond. Nat Rev Immunol. 2016 Apr; 16(4):247-58. PMID: 26972725.
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LaFlam TN, Seumois G, Miller CN, Lwin W, Fasano KJ, Waterfield M, Proekt I, Vijayanand P, Anderson MS. Identification of a novel cis-regulatory element essential for immune tolerance. J Exp Med. 2015 Nov 16; 212(12):1993-2002. PMID: 26527800.
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Anderson MS, Mackay F. Editorial overview: Autoimmunity. Curr Opin Immunol. 2015 Dec; 37:v-vii. PMID: 26510378.
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Khan IS, Park CY, Mavropoulos A, Shariat N, Pollack JL, Barczak AJ, Erle DJ, McManus MT, Anderson MS, Jeker LT. Identification of MiR-205 As a MicroRNA That Is Highly Expressed in Medullary Thymic Epithelial Cells. PLoS One. 2015; 10(8):e0135440. PMID: 26270036.
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Yoshida H, Bansal K, Schaefer U, Chapman T, Rioja I, Proekt I, Anderson MS, Prinjha RK, Tarakhovsky A, Benoist C, Mathis D. Brd4 bridges the transcriptional regulators, Aire and P-TEFb, to promote elongation of peripheral-tissue antigen transcripts in thymic stromal cells. Proc Natl Acad Sci U S A. 2015 Aug 11; 112(32):E4448-57. PMID: 26216992.
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Landegren N, Sharon D, Shum AK, Khan IS, Fasano KJ, Hallgren Å, Kampf C, Freyhult E, Ardesjö-Lundgren B, Alimohammadi M, Rathsman S, Ludvigsson JF, Lundh D, Motrich R, Rivero V, Fong L, Giwercman A, Gustafsson J, Perheentupa J, Husebye ES, Anderson MS, Snyder M, Kämpe O. Transglutaminase 4 as a prostate autoantigen in male subfertility. Sci Transl Med. 2015 Jun 17; 7(292):292ra101. PMID: 26084804.
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Anderson MS, Casanova JL. More than Meets the Eye: Monogenic Autoimmunity Strikes Again. Immunity. 2015 Jun 16; 42(6):986-8. PMID: 26084018.
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Su MA, Anderson MS. Breaking through the central tolerance ceiling to unleash anticancer immune responses. Oncoimmunology. 2014; 3(8):e950169. PMID: 25610739.
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Khan IS, Mouchess ML, Zhu ML, Conley B, Fasano KJ, Hou Y, Fong L, Su MA, Anderson MS. Enhancement of an anti-tumor immune response by transient blockade of central T cell tolerance. J Exp Med. 2014 May 05; 211(5):761-8. PMID: 24752296.
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Chen YF, Zhou D, Metzger T, Gallup M, Jeanne M, Gould DB, Anderson MS, McNamara NA. Spontaneous development of autoimmune uveitis Is CCR2 dependent. Am J Pathol. 2014 Jun; 184(6):1695-705. PMID: 24736166.
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Khan IS, Taniguchi RT, Fasano KJ, Anderson MS, Jeker LT. Canonical microRNAs in thymic epithelial cells promote central tolerance. Eur J Immunol. 2014 May; 44(5):1313-9. PMID: 24515814.
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Waterfield M, Khan IS, Cortez JT, Fan U, Metzger T, Greer A, Fasano K, Martinez-Llordella M, Pollack JL, Erle DJ, Su M, Anderson MS. The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance. Nat Immunol. 2014 Mar; 15(3):258-65. PMID: 24464130.
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Shum AK, Alimohammadi M, Tan CL, Cheng MH, Metzger TC, Law CS, Lwin W, Perheentupa J, Bour-Jordan H, Carel JC, Husebye ES, De Luca F, Janson C, Sargur R, Dubois N, Kajosaari M, Wolters PJ, Chapman HA, Kämpe O, Anderson MS. BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease. Sci Transl Med. 2013 Oct 09; 5(206):206ra139. PMID: 24107778.
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Metzger TC, Khan IS, Gardner JM, Mouchess ML, Johannes KP, Krawisz AK, Skrzypczynska KM, Anderson MS. Lineage tracing and cell ablation identify a post-Aire-expressing thymic epithelial cell population. Cell Rep. 2013 Oct 17; 5(1):166-79. PMID: 24095736.
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Gardner JM, Metzger TC, McMahon EJ, Au-Yeung BB, Krawisz AK, Lu W, Price JD, Johannes KP, Satpathy AT, Murphy KM, Tarbell KV, Weiss A, Anderson MS. Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4? T cells. Immunity. 2013 Sep 19; 39(3):560-72. PMID: 23993652.
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Cheng MH, Anderson MS. Insights into type 1 diabetes from the autoimmune polyendocrine syndromes. Curr Opin Endocrinol Diabetes Obes. 2013 Aug; 20(4):271-8. PMID: 23770732.
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Parent AV, Russ HA, Khan IS, LaFlam TN, Metzger TC, Anderson MS, Hebrok M. Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development. Cell Stem Cell. 2013 Aug 01; 13(2):219-29. PMID: 23684540.
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Breunig A, Lee MS, Miller BS, Binstadt BA, Anderson MS, Montezuma S. Autoimmune retinopathy in a patient with autoimmune polyendocrine syndrome type I. Ocul Immunol Inflamm. 2013 Apr; 21(2):153-7. PMID: 23697860.
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Taniguchi RT, DeVoss JJ, Moon JJ, Sidney J, Sette A, Jenkins MK, Anderson MS. Detection of an autoreactive T-cell population within the polyclonal repertoire that undergoes distinct autoimmune regulator (Aire)-mediated selection. Proc Natl Acad Sci U S A. 2012 May 15; 109(20):7847-52. PMID: 22552229.
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Su MA, Davini D, Cheng P, Giang K, Fan U, DeVoss JJ, Johannes KP, Taylor L, Shum AK, Valenzise M, Meloni A, Bour-Jordan H, Anderson MS. Defective autoimmune regulator-dependent central tolerance to myelin protein zero is linked to autoimmune peripheral neuropathy. J Immunol. 2012 May 15; 188(10):4906-12. PMID: 22490868.
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Cheng MH, Anderson MS. Monogenic autoimmunity. Annu Rev Immunol. 2012; 30:393-427. PMID: 22224765.
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Waterfield M, Anderson MS. Autoimmunity's collateral damage: Immunodeficiency hints at autoreactivity to cytokines. Nat Med. 2011 Sep 07; 17(9):1054-5. PMID: 21900922.
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Metzger TC, Anderson MS. Control of central and peripheral tolerance by Aire. Immunol Rev. 2011 May; 241(1):89-103. PMID: 21488892.
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Metzger TC, Anderson MS. Myocarditis: a defect in central immune tolerance? J Clin Invest. 2011 Apr; 121(4):1251-3. PMID: 21436581.
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Anderson MS, Su MA. Aire and T cell development. Curr Opin Immunol. 2011 Apr; 23(2):198-206. PMID: 21163636.
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Taniguchi RT, Anderson MS. The role of Aire in clonal selection. Immunol Cell Biol. 2011 Jan; 89(1):40-4. PMID: 21079643.
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Waterfield M, Anderson MS. Clues to immune tolerance: the monogenic autoimmune syndromes. Ann N Y Acad Sci. 2010 Dec; 1214:138-55. PMID: 20969580.
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Husebye ES, Anderson MS. Autoimmune polyendocrine syndromes: clues to type 1 diabetes pathogenesis. Immunity. 2010 Apr 23; 32(4):479-87. PMID: 20412758.
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DeVoss JJ, LeClair NP, Hou Y, Grewal NK, Johannes KP, Lu W, Yang T, Meagher C, Fong L, Strauss EC, Anderson MS. An autoimmune response to odorant binding protein 1a is associated with dry eye in the Aire-deficient mouse. J Immunol. 2010 Apr 15; 184(8):4236-46. PMID: 20237294.
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Shum AK, DeVoss J, Tan CL, Hou Y, Johannes K, O'Gorman CS, Jones KD, Sochett EB, Fong L, Anderson MS. Identification of an autoantigen demonstrates a link between interstitial lung disease and a defect in central tolerance. Sci Transl Med. 2009 Dec 02; 1(9):9ra20. PMID: 20368189.
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Gardner JM, Fletcher AL, Anderson MS, Turley SJ. AIRE in the thymus and beyond. Curr Opin Immunol. 2009 Dec; 21(6):582-9. PMID: 19833494.
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Hou Y, DeVoss J, Dao V, Kwek S, Simko JP, McNeel DG, Anderson MS, Fong L. An aberrant prostate antigen-specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans. J Clin Invest. 2009 Jul; 119(7):2031-41. PMID: 19603556.
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Su MA, Anderson MS. Monogenic autoimmune diseases: insights into self-tolerance. Pediatr Res. 2009 May; 65(5 Pt 2):20R-25R. PMID: 19190526.
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Louvet C, Kabre BG, Davini DW, Martinier N, Su MA, DeVoss JJ, Rosenthal WL, Anderson MS, Bour-Jordan H, Bluestone JA. A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy. J Exp Med. 2009 Mar 16; 206(3):507-14. PMID: 19221395.
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Su MA, Stenerson M, Liu W, Putnam A, Conte F, Bluestone JA, Anderson MS. The role of X-linked FOXP3 in the autoimmune susceptibility of Turner Syndrome patients. Clin Immunol. 2009 Apr; 131(1):139-44. PMID: 19150256.
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Anderson MS. Update in endocrine autoimmunity. J Clin Endocrinol Metab. 2008 Oct; 93(10):3663-70. PMID: 18842982.
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Devoss JJ, Shum AK, Johannes KP, Lu W, Krawisz AK, Wang P, Yang T, Leclair NP, Austin C, Strauss EC, Anderson MS. Effector mechanisms of the autoimmune syndrome in the murine model of autoimmune polyglandular syndrome type 1. J Immunol. 2008 Sep 15; 181(6):4072-9. PMID: 18768863.
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Zhou X, Jeker LT, Fife BT, Zhu S, Anderson MS, McManus MT, Bluestone JA. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med. 2008 Sep 01; 205(9):1983-91. PMID: 18725525.
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Gardner JM, Devoss JJ, Friedman RS, Wong DJ, Tan YX, Zhou X, Johannes KP, Su MA, Chang HY, Krummel MF, Anderson MS. Deletional tolerance mediated by extrathymic Aire-expressing cells. Science. 2008 Aug 08; 321(5890):843-7. PMID: 18687966.
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Su MA, Giang K, Zumer K, Jiang H, Oven I, Rinn JL, Devoss JJ, Johannes KP, Lu W, Gardner J, Chang A, Bubulya P, Chang HY, Peterlin BM, Anderson MS. Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in Aire. J Clin Invest. 2008 May; 118(5):1712-26. PMID: 18414681.
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Schaller CE, Wang CL, Beck-Engeser G, Goss L, Scott HS, Anderson MS, Wabl M. Expression of Aire and the early wave of apoptosis in spermatogenesis. J Immunol. 2008 Feb 01; 180(3):1338-43. PMID: 18209027.
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Li S, Nikulina K, DeVoss J, Wu AJ, Strauss EC, Anderson MS, McNamara NA. Small proline-rich protein 1B (SPRR1B) is a biomarker for squamous metaplasia in dry eye disease. Invest Ophthalmol Vis Sci. 2008 Jan; 49(1):34-41. PMID: 18172072.
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Zhang L, Barker JM, Babu S, Su M, Stenerson M, Cheng M, Shum A, Zamir E, Badolato R, Law A, Eisenbarth GS, Anderson MS. A robust immunoassay for anti-interferon autoantibodies that is highly specific for patients with autoimmune polyglandular syndrome type 1. Clin Immunol. 2007 Nov; 125(2):131-7. PMID: 17825626.
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Cheng MH, Shum AK, Anderson MS. What's new in the Aire? Trends Immunol. 2007 Jul; 28(7):321-7. PMID: 17556019.
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DeVoss JJ, Anderson MS. Lessons on immune tolerance from the monogenic disease APS1. Curr Opin Genet Dev. 2007 Jun; 17(3):193-200. PMID: 17466510.
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DeVoss J, Hou Y, Johannes K, Lu W, Liou GI, Rinn J, Chang H, Caspi RR, Caspi R, Fong L, Anderson MS. Spontaneous autoimmunity prevented by thymic expression of a single self-antigen. J Exp Med. 2006 Nov 27; 203(12):2727-35. PMID: 17116738.
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Anderson MS, Venanzi ES, Chen Z, Berzins SP, Benoist C, Mathis D. The cellular mechanism of Aire control of T cell tolerance. Immunity. 2005 Aug; 23(2):227-39. PMID: 16111640.
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Anderson MS, Bluestone JA. The NOD mouse: a model of immune dysregulation. Annu Rev Immunol. 2005; 23:447-85. PMID: 15771578.
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Su MA, Anderson MS. Aire: an update. Curr Opin Immunol. 2004 Dec; 16(6):746-52. PMID: 15511668.
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Anderson MS. Autoimmune endocrine disease. Curr Opin Immunol. 2002 Dec; 14(6):760-4. PMID: 12413526.
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Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D. Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002 Nov 15; 298(5597):1395-401. PMID: 12376594.
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Anderson MS, Swier K, Arneson L, Miller J. Enhanced antigen presentation in the absence of the invariant chain endosomal localization signal. J Exp Med. 1993 Dec 01; 178(6):1959-69. PMID: 7902408.
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Anderson MS, Miller J. Invariant chain can function as a chaperone protein for class II major histocompatibility complex molecules. Proc Natl Acad Sci U S A. 1992 Mar 15; 89(6):2282-6. PMID: 1549594.
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